Gao Ai-Mei, Zhang Xiao-Yu, Ke Zun-Ping
Department of Pharmacy, The Fifth People's Hospital of Shanghai, Fudan University, Shanghai, China.
Department of Clinical Pharmacy, Shanghai General Hospital, Shanghai Jiaotong University School of Medicine, Shanghai, China.
Oncotarget. 2017 May 30;8(47):82085-82091. doi: 10.18632/oncotarget.18294. eCollection 2017 Oct 10.
Chemo-resistance is one of the main obstacle in hepatocellular carcinoma therapy. Apigenin as a natural bioflavonoid has been exhibited anti-cancer properties in various malignant cancers. The aim of this study is to evaluate the potential chemo-sensitization effect of apigenin in doxorubicin-resistant hepatocellular carcinoma cell line BEL-7402/ADM and to investigate its possible mechanism. We found that apigenin significantly reversed doxorubicin sensitivity and induced caspase-dependent apoptosis in BEL-7402/ADM cells. Furthermore, apigenin induced miR-101 expression, and overexpression of miR-101 mimicked the doxorubicin-sensitizing effect of apigenin. Importantly, we showed that miR-101 was able to target the 3'-UTR of Nrf2. The results suggested that apigenin sensitizes BEL-7402/ADM cells to doxorubicin through miR-101/Nrf2 pathway, which furtherly supports apigenin as a potential chemo-sensitizer for hepatocellular carcinoma.
化疗耐药是肝细胞癌治疗的主要障碍之一。芹菜素作为一种天然生物类黄酮，已在多种恶性肿瘤中表现出抗癌特性。本研究旨在评估芹菜素对阿霉素耐药的肝癌细胞系BEL-7402/ADM的潜在化疗增敏作用，并探讨其可能机制。我们发现芹菜素显著逆转了BEL-7402/ADM细胞对阿霉素的敏感性，并诱导了依赖半胱天冬酶的凋亡。此外，芹菜素诱导miR-101表达，miR-101的过表达模拟了芹菜素的阿霉素增敏作用。重要的是，我们表明miR-101能够靶向Nrf2的3'-UTR。结果表明，芹菜素通过miR-101/Nrf2途径使BEL-7402/ADM细胞对阿霉素敏感，这进一步支持芹菜素作为肝癌潜在的化疗增敏剂。
